This proposed work seeks to determine the relative contribution of factors in the central nervous system to the control of breathing in chronic states of hypoxia and acid-base imbalance. Major studies within this aim include those aimed at: a) the role of intra- and extracellular fluid brain (H+) using ventricular-cisternal perfusion in awake animals; b) the role of brain neurotransmitters on eupnea; and c) the interaction of various chronic stimuli and depressants on the control of breathing during slow-wave sleep in humans.